Multiscale simulation-guided enzyme nanostructure design for catalysis enhancement

Enzyme catalysis incorporated into pharmaceutical or chemical manufacturing can be environmentally more friendly and efficient than traditional synthesis with solely organic and inorganic reagents. Chemical conjugation of DNA, protein, or polymer scaffolds to an enzyme is a widely used strategy to enhance enzyme stability and activity. A central challenge in the design of such systems is a fundamental understanding of the effects of scaffold position on the desired enzyme property. In this presentation, we will talk about using a combined computational (i.e. Brownian dynamics and molecular dynamics simulations), biophysical theories and experimental approach to develop and validate a predictive model for biocatalytic activity enhancement. We will discuss a significant advantage in catalytic enhancement by optimizing the scaffold colocalized, which also provides the intermediate a diffusive advantage that enhanced substrate transfer probability. We also show that the substrate concentration can be increased locally by chemical conjugation of DNAs which also contributes to overall rate enhancement. The results highlight the importance of the non-specific intermolecular attractions and effective substrate concentration in catalysis. They shed light on strategies for engineering multienzyme and/or conjugated nanostructures for various applications.